Mechanisms of Platelet Activation and Integrin alphaIIbeta3.
10.4070/kcj.2012.42.5.295
- Author:
Seung Jae JOO
1
Author Information
1. Cardiology Division, Department of Internal Medicine, Jeju National University Hospital, Jeju, Korea. sejjoo@jejunu.ac.kr
- Publication Type:Review
- Keywords:
Platelet activation;
Receptors, G-protein-coupled;
Integrin alpha-IIb beta-3
- MeSH:
Acute Coronary Syndrome;
Adenosine Diphosphate;
Blood Platelets;
Calcium Signaling;
Cytoplasm;
Fibrinogen;
Guanine Nucleotide Exchange Factors;
Hemostasis;
Ligands;
Phosphatidylinositol 3-Kinase;
Platelet Activation;
Platelet Aggregation;
Platelet Glycoprotein GPIIb-IIIa Complex;
Protein Kinase C;
Proteins;
Receptors, G-Protein-Coupled;
Stroke;
Thrombin;
Thromboxane A2;
Type C Phospholipases;
von Willebrand Factor
- From:Korean Circulation Journal
2012;42(5):295-301
- CountryRepublic of Korea
- Language:English
-
Abstract:
Platelet aggregation is not only an essential part of hemostasis, but also initiates acute coronary syndrome or ischemic stroke. The precise understanding of the activation mechanism of platelet aggregation is fundamental for the development of more effective agents against platelet aggregation. Adenosine diphosphate, thrombin, and thromboxane A2 activate platelet integrin alphaIIbbeta3 through G protein-coupled receptors. G protein-mediated signaling pathways, which are initiated by Gq, G12/G13 or Gi, include phospholipase C with calcium signaling, Rho signaling, protein kinase C and phosphatidylinositol 3-kinase. Rap1b, Ca2+ and diacylglycerol-regulated guanine nucleotide exchange factor I, Rap1-GTP-interacting adaptor molecule, and Akt are important proteins involved in G protein-mediated activation of integrin alphaIIbbeta3. Binding of talin-1 and kindlin-3 to cytoplasmic domains of beta3-integrin triggers a conformational change in the extracellular domains that increases its affinity for ligands, such as fibrinogen or von Willebrand factor. Fibrinogens act as bridges between adjacent platelets to generate a platelet aggregate.
